The POU domain transcription factor Brn-2: elevated expression in malignant melanoma and regulation of melanocyte-specific gene expression

Oncogene. 1995 Nov 16;11(10):2157-64.


Previous work has shown that melanoma cell lines express a distinct octamer binding protein. Given the role of octamer-binding proteins in cell differentiation and development, the role this factor is a key issue in understanding melanocyte differentiation and transformation. Using a proteolytic clipping assay, we show that the melanoma-specific octamer factor is Brn-2/N-Oct3, a POU domain protein previously known to be expressed in adult brain and in the developing nervous system. N-Oct3 mRNA was detected in a range of human melanoma cell lines and was around 10-fold elevated compared to normal human melanocytes while mRNA for Brn-2 was also detected in a mouse melanoblast cell line. Expression of Brn-2/N-Oct3, in melanoma cells in cotransfection assays activated the expression of the MHC class II DR alpha promoter but repressed the activity of the melanocyte-specific tyrosinase promoter. Repression correlated with Brn-2/N-Oct3 binding in a mutually exclusive fashion with basic-helix-loop-helix-leucine-zipper (bHLH-LZ) transcription factor USF in vitro and with Brn-2 expression preventing activation of the tyrosinase promoter by the bHLH-LZ factor Microphthalmia in vivo. The potential role of Brn-2/N-Oct3 in melanocyte differentiation and gene expression is discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • Base Sequence
  • Binding Sites
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic
  • HLA-DR Antigens / genetics
  • Helix-Loop-Helix Motifs / physiology
  • Homeodomain Proteins
  • Humans
  • Melanocytes / metabolism
  • Melanocytes / physiology*
  • Melanoma / genetics*
  • Melanoma / metabolism*
  • Melanoma-Specific Antigens
  • Molecular Sequence Data
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • POU Domain Factors
  • Promoter Regions, Genetic / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transfection
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • DNA, Neoplasm
  • HLA-DR Antigens
  • Homeodomain Proteins
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • POU Domain Factors
  • RNA, Messenger
  • Transcription Factors
  • transcription factor Brn-2
  • Monophenol Monooxygenase